Jenny Kaelyn A, Mose Gracyn, Haupt Daniel J, Hondal Robert J
Room B413, Given Laboratory, Department of Biochemistry, College of Medicine, University of Vermont, 89 Beaumont Ave, Burlington, VT 05405, USA.
Room E340, Innovation Hall, Department of Chemistry, University of Vermont, 82 University Place, Burlington, VT 05405, USA.
Antioxidants (Basel). 2022 Jan 19;11(2):185. doi: 10.3390/antiox11020185.
Ergothioneine (EGT) is a sulfur-containing amino acid analog that is biosynthesized in fungi and bacteria, accumulated in plants, and ingested by humans where it is concentrated in tissues under oxidative stress. While the physiological function of EGT is not yet fully understood, EGT is a potent antioxidant in vitro. Here we report that oxidized forms of EGT, EGT-disulfide (ESSE) and 5-oxo-EGT, can be reduced by the selenoenzyme mammalian thioredoxin reductase (Sec-TrxR). ESSE and 5-oxo-EGT are formed upon reaction with biologically relevant reactive oxygen species. We found that glutathione reductase (GR) can reduce ESSE, but only with the aid of glutathione (GSH). The reduction of ESSE by TrxR was found to be selenium dependent, with non-selenium-containing TrxR enzymes having little or no ability to reduce ESSE. In comparing the reduction of ESSE by Sec-TrxR in the presence of thioredoxin to that of GR/GSH, we find that the glutathione system is 10-fold more efficient, but Sec-TrxR has the advantage of being able to reduce both ESSE and 5-oxo-EGT directly. This represents the first discovered direct enzymatic recycling system for oxidized forms of EGT. Based on our in vitro results, the thioredoxin system may be important for EGT redox biology and requires further in vivo investigation.
麦角硫因（EGT）是一种含硫氨基酸类似物，在真菌和细菌中生物合成，在植物中积累，并被人类摄入，在氧化应激下它会在组织中富集。虽然EGT的生理功能尚未完全了解，但EGT在体外是一种有效的抗氧化剂。在此我们报告，EGT的氧化形式，即EGT-二硫化物（ESSE）和5-氧代-EGT，可以被硒酶哺乳动物硫氧还蛋白还原酶（Sec-TrxR）还原。ESSE和5-氧代-EGT是在与生物相关的活性氧反应时形成的。我们发现谷胱甘肽还原酶（GR）可以还原ESSE，但仅在谷胱甘肽（GSH）的帮助下。发现TrxR对ESSE的还原是硒依赖性的，不含硒的TrxR酶几乎没有或完全没有还原ESSE的能力。在比较Sec-TrxR在硫氧还蛋白存在下对ESSE的还原与GR/GSH对ESSE的还原时，我们发现谷胱甘肽系统的效率高10倍，但Sec-TrxR的优势在于能够直接还原ESSE和5-氧代-EGT。这代表了首次发现的EGT氧化形式的直接酶促循环系统。基于我们的体外结果，硫氧还蛋白系统可能对EGT氧化还原生物学很重要，需要进一步进行体内研究。
